Antibody against inhibin and use thereof

Abstract

An anti-inhibin antibody and its applications are provided. The antibody can have the inhibitory effect of inhibins on the secretion of endogenous follicle-stimulating hormone (FSH), promote the secretion of endogenous FSH and promote the development of animal follicles. The antibody can replace the use of FSH or pregnant mare serum Gonadotropin (PMSG) in animal reproduction, and can be used for promoting animal reproduction, estrus synchronization, conception and birth, embryo transferring, improving ovulation quality, promoting livestock reproduction, and inducing estrus in female livestock.

What is claimed is: 
     
         1 . An anti-inhibin antibody or antigen-binding portion thereof, comprising a combination of CDRs selected from heavy chain and light chain below:
 (1) heavy chain CDR1, CDR2 and CDR3 comprising the sequences of SEQ ID NO: 1, 2, 3 or any variant thereof respectively, and light chain CDR1, CDR2 and CDR3 comprising the sequences of SEQ ID NO: 4, 5, 6 or any variant thereof respectively;   (2) heavy chain CDR1, CDR2 and CDR3 comprising the sequences of SEQ ID NO: 11, 12, 13 or any variant thereof respectively, and light chain CDR1, CDR2 and CDR3 comprising the sequences of SEQ ID NO.14, 15, 16 or any variant thereof respectively;   preferably, the antibody or antigen-binding portion thereof comprises a heavy chain variable region having the amino acid sequence selected from SEQ ID NO: 7, 17 or any variant thereof, and a light chain variable region having the amino acid sequence selected from SEQ ID NO: 9, 19 or any variant thereof.   
     
     
         2 . The anti-inhibin antibody or antigen-binding portion thereof of  claim 1 , comprising the heavy chain variable region having the amino acid sequence of SEQ ID NO: 7 or any variant thereof, and the light chain variable region having the amino acid sequence of SEQ ID NO: 9 or any variant thereof. 
     
     
         3 . The anti-inhibin antibody or antigen-binding portion thereof of  claim 1 , comprising the heavy chain variable region having the amino acid sequence of SEQ ID NO: 17 or any variant thereof, and the light chain variable region having the amino acid sequence of SEQ ID NO: 19 or any variant thereof. 
     
     
         4 . Nucleic acid molecule encoding the anti-inhibin antibody or antigen-binding portion thereof of  claim 1 ;
 preferably, the nucleic acid molecule comprises a nucleic acid sequence selected from SEQ ID NO: 8, 18 or any variant thereof that encodes an antibody heavy chain variable region, and a nucleic acid sequence selected from SEQ ID NO: 10, 20 or any variant thereof that encodes an antibody light chain variable region;   more preferably, the nucleic acid molecule comprises a nucleic acid sequence shown in SEQ ID NO: 8 or any variant thereof that encodes a heavy chain variable region, and a nucleic acid sequence shown in SEQ ID NO: 10 or any variant thereof that encodes a light chain variable region;   more preferably, the nucleic acid molecule comprises a nucleic acid sequence shown in SEQ ID NO: 18 or any variant thereof that encodes a heavy chain variable region, and a nucleic acid sequence shown in SEQ ID NO: 20 or any variant thereof that encodes a light chain variable region.   
     
     
         5 . A vector comprising the nucleic acid molecule of  claim 4 . 
     
     
         6 . A cell comprising the nucleic acid of  claim 4  or the vector comprising the nucleic acid molecule. 
     
     
         7 . An expression system, which is constructed by introducing an expression vector comprising the nucleic acid of  claim 4  into a host cell;
 the expression vector comprises any one selected from bacterial plasmids, yeast plasmids, plant cell viruses and mammalian cell viruses (such as adenovirus or retrovirus); more preferably, the expression vector is pcDNA3.1(+); 
 the host cell is a prokaryotic host cell or a eukaryotic host cell; 
 preferably, the prokaryotic host cell is a bacterial cell; preferably, the bacterial cell is  Escherichia coli;    
 preferably, the eukaryotic host cell is selected from any one of fungi, plants, insects and mammals; 
 preferably, the fungal eukaryotic host cell is selected from any one of yeast (such as  Pichia pastoris  and  Saccharomyces cerevisiae ) and filamentous fungi; 
 preferably, the mammalian eukaryotic host cell is selected from any one of Chinese hamster ovary (CHO) cells, murine myeloma (NSO) cells, baby hamster kidney (BHK) cells and human embryonic kidney (HEK) cells (such as HEK293 cells); more preferably, the host cell is the Chinese hamster ovary (CHO) cells. 
 
     
     
         8 . The expression system of  claim 7 , wherein the method of introducing the expression vector into the host cell is selected from transfection, transformation or infection;
 preferably, the expression vector is introduced into the host cell by transfection;   preferably, the transfection includes: electroporation transfection, calcium phosphate transfection, liposome transfection, protoplast fusion transfection, microinjection, electroporation, gene gun, cationic polymer and viral vector infection.   
     
     
         9 . A composition comprising the antibody or antigen-binding portion thereof of  claim 1 , the nucleic acid encoding the anti-inhibin antibody or antigen-binding portion thereof, the vector comprising the nucleic acid, and/or the cell comprising the nucleic acid or the vector. 
     
     
         10 . Use of the anti-inhibin antibody or antigen-binding portion thereof of  claim 1 , the nucleic acid encoding the anti-inhibin antibody or antigen-binding portion thereof, the vector comprising the nucleic acid, the cell comprising the nucleic acid or the vector and/or a composition in the preparation of medications for promoting animal reproduction, estrus synchronization, conception and birth, embryo transfer, improving ovulation quality, promoting livestock reproduction, or inducing estrus in female livestock, wherein the composition comprising the antibody or antigen-binding portion thereof of  claim 1 , the nucleic acid encoding the anti-inhibin antibody or antigen-binding portion thereof, the vector comprising the nucleic acid, and/or the cell comprising the nucleic acid or the vector;
 preferably, the animals are thereof selected from mice, pigs, cattle, goat.   
     
     
         11 . A method for promoting animal reproduction, estrus synchronization, conception and birth, embryo transfer, improving ovulation quality, promoting livestock reproduction, or inducing estrus in female livestock, comprising administering the anti-inhibin antibody or antigen-binding portion thereof of  claim 1 ,
 wherein the anti-inhibin antibody or antigen-binding portion thereof is administered at a dose of 0.1-1,000 μg/kg, and   wherein the administration of the anti-inhibin antibody or antigen-binding portion thereof is by intraperitoneal, intramuscular or subcutaneous injection.   
     
     
         12 . An anti-inhibin antibody or antigen-binding portion thereof, comprising a combination of CDRs selected from heavy chain and light chain below:
 (1) heavy chain CDR1, CDR2 and CDR3 comprising the sequences which are at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the amino acid sequences of SEQ ID NO: 1, 2, 3 respectively, and light chain CDR1, CDR2 and CDR3 comprising the sequences which are at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the amino acid sequences of SEQ ID NO: 4, 5, 6 respectively;   (2) heavy chain CDR1, CDR2 and CDR3 comprising the sequences which are at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the amino acid sequences of SEQ ID NO: 11, 12, 13 respectively, and light chain CDR1, CDR2 and CDR3 comprising the sequences which are at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the amino acid sequences of SEQ ID NO: 14, 15, 16 respectively,   wherein the antibody or antigen-binding portion thereof comprises a heavy chain variable region having the amino acid sequence which is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the amino acid sequence selected from SEQ ID NO: 7, 17, and a light chain variable region having the amino acid sequence which is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the amino acid sequence selected from SEQ ID NO: 9, 19.   
     
     
         13 . Nucleic acid molecule comprising a nucleic acid sequence which is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the nucleic acid sequence selected from SEQ ID NO: 8, 18 that encodes an antibody heavy chain variable region, and a nucleic acid sequence which is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the nucleic acid sequence selected from SEQ ID NO: 10, 20 that encodes an antibody light chain variable region,
 wherein the nucleic acid molecule comprises a nucleic acid sequence which is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the nucleic acid sequence shown in SEQ ID NO: 8 that encodes a heavy chain variable region, and a nucleic acid sequence which is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the nucleic acid sequence shown in SEQ ID NO: 10 that encodes a light chain variable region, or   wherein the nucleic acid molecule comprises a nucleic acid sequence which is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the nucleic acid sequence shown in SEQ ID NO. 18 that encodes a heavy chain variable region, and a nucleic acid sequence which is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or higher homologous to the nucleic acid sequence shown in SEQ ID NO: 20 that encodes a light chain variable region.